We are investigating the effects of prednisolone and d-penicillamine on the natural history of acute alcoholic liver disease (ALD). In our initial studies, patients with ALD were grouped into three categories based on increasing severity of the disease. Patients in group A all have hepatomegaly, clinically evident jaundice (bilirubin greater than 3 mg/dl) and liver biopsy evidence of acute alcoholic liver disease. Group B patients have in addition to jaundice, hepatomegaly, and liver biopsy evidence of acute ALD, either ascites or hepatic encephalopathy. Patients in group C have more severe disease with persistent coagulation abnormalities precluding liver biopsy. All patients are hosptialized for 5 to 6 weeks. Assessments are made of mortality, overall mobidity and incidence of side effects during therapy. All patients in groups A and B have liver biopsies before and after the therapeutic trial. Before and after therapy we assess: 1. liver function tests; 2. wedged hepatic venous pressure as an index of portal hypertension; 3. wedged & dree hepatic venograms as an index of the status of intrahepatic vasculature; 4. plasma volume by I125 labeled albumin; 5. BSP storage and maximum excretory capacity; 6. fibrogenesis by determination of protocollagen proline hydroxylase on liver biopsy specimens and urinary hydroxproline excretion. In the second phase of our studies we are comparing d-penicillamines versus placebo in patients with acute ALD. A similar protocol is utilized in these studies with the addition of determination of hepatic copper content on liver biopsies before and after treatment. Histologic evaluations of treatment effects from both trials are performed by Wilcoxon rank sum analysis. BIBLIOGRAPHIC REFERENCES: Mitch, W., Whelton, P.K., Cooke, C.R., Walker, W.G., and Maddrey, W.C.: Hepatic renin and aldosterone extraction in alcoholic hepatic disease: Effect of prednisolone therapy. Clin. Res., 1977 (In Press). Maddrey, W.C., Boitnott, J.K., Bedine, M.S., Weber, F.L., and Mezey, E.: Corticosteroid treatment of alcoholic liver disease: A controlled trial Gastroent., 1977 (In Press).